This new application is part of the competitive renewal for the "Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)". One of the overall goals of the entire CIFASD during this renewal period is to determine if innovative techniques can be used to identify brain alterations, neurobehavioral deficits and facial characteristics and relationships between these variables to help define prenatal alcohol spectrum disorders (FASD). To help address this overarching question, we will use quantitative brain mapping techniques with high-resolution structural and functional MRI collected both cross-sectionally and longitudinally from 80 FASD children evaluated across 3 multi-cultural data collection sites (San Diego, Los Angeles and Capetown, South Africa). While this brain imaging project can independently achieve some of the goals of the CIFASD by identifying brain structural and functional abnormalities across the broad spectrum of FASD, critically this funding opportunity will allow the assessment of relationships between the brain, neurocognitive deficits and facial dysmorphology through our active collaborations with the neurobehavioral project (Mattson PI), the facial imaging project (Foroud PI), and the dysmorphology core (Jones PI). Controlled animal studies are essential to determine timing and dosages of prenatal alcohol that result in FASD, but human imaging studies are essential to corroborate anatomical findings across species. Through our association with the UCLA Laboratory of Neuro Imaging, we have access to state-of-the-art brain mapping tools that allow the morphological evaluation of any brain structure that can be identified with MRI. Thus, we are in a unique position to allow findings in animal studies to drive hypothesis-based analyses in the human imaging data. The proposed longitudinal project will highlight how an integrated approach relating neurobehavioral, functional and structural brain imaging data, and measures of facial morphology might yield important new insights on the complex nature of brain-behavior interactions and how they are altered by prenatal alcohol exposure. To our knowledge, this will be the first study to undertake such challenges, and participation, in the CIFASD is essential to address our specific aims. Ultimately, as part of the CIFASD, this project will enhance the capability for definitive FASD diagnoses that, in turn, will help clinicians manage and treat neurobehavioral deficits and associated secondary disabilities. [unreadable] [unreadable] [unreadable]